MCID: LYS017
MIFTS: 38

Loeys-Dietz Syndrome 4

Categories: Genetic diseases, Rare diseases, Bone diseases

Aliases & Classifications for Loeys-Dietz Syndrome 4

MalaCards integrated aliases for Loeys-Dietz Syndrome 4:

Name: Loeys-Dietz Syndrome 4 57 53 75 29 6 73
Lds4 57 75
Aneurysm, Aortic and Cerebral, with Arterial Tortuosity and Skeletal Manifestations 57
Aortic and Cerebral Aneurysm with Arterial Tortuosity and Skeletal Manifestations 75
Syndrome, Loeys-Dietz, Type 4 40
Loeys-Dietz Syndrome, Type 4 13
Loeys-Dietz Syndrome Type 4 53

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
patients do not have ectopia lentis


HPO:

32
loeys-dietz syndrome 4:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Loeys-Dietz Syndrome 4

UniProtKB/Swiss-Prot : 75 Loeys-Dietz syndrome 4: An aortic aneurysm syndrome with widespread systemic involvement. LDS4 is characterized by arterial tortuosity, aortic dissection, intracranial aneurysm and subarachnoid hemorrhage, hypertelorism, bifid uvula, pectus deformity, bicuspid aortic valve, arachnodactyly, scoliosis, foot deformities, dural ectasia, joint hyperflexibility, and thin skin with easy bruising and striae.

MalaCards based summary : Loeys-Dietz Syndrome 4, also known as lds4, is related to loeys-dietz syndrome and multilocular clear cell renal cell carcinoma, and has symptoms including wrist sign and steinberg thumb sign. An important gene associated with Loeys-Dietz Syndrome 4 is TGFB2 (Transforming Growth Factor Beta 2), and among its related pathways/superpathways are ErbB signaling pathway and Human Embryonic Stem Cell Pluripotency. Affiliated tissues include skin, and related phenotypes are hypertelorism and high palate

Description from OMIM: 614816

Related Diseases for Loeys-Dietz Syndrome 4

Diseases related to Loeys-Dietz Syndrome 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 loeys-dietz syndrome 28.9 TGFB2 TGFB3
2 multilocular clear cell renal cell carcinoma 9.4 TGFB2 TGFB3
3 tuberculoid leprosy 9.3 TGFB2 TGFB3
4 peyronie's disease 9.2 TGFB2 TGFB3
5 mitral valve disease 9.1 TGFB2 TGFB3

Graphical network of the top 20 diseases related to Loeys-Dietz Syndrome 4:



Diseases related to Loeys-Dietz Syndrome 4

Symptoms & Phenotypes for Loeys-Dietz Syndrome 4

Symptoms via clinical synopsis from OMIM:

57
Skeletal Spine:
scoliosis
spondylolisthesis (rare)

Genitourinary External Genitalia Female:
inguinal hernia

Skeletal:
joint hyperflexibility
tall stature

Skeletal Hands:
arachnodactyly
steinberg thumb sign

Neurologic Central Nervous System:
dural ectasia

Head And Neck Mouth:
high-arched palate
broad or bifid uvula (in some patients)

Skin Nails Hair Skin:
easy bruising
skin striae

Respiratory Lung:
emphysema (rare)
pneumothorax (rare)

Skeletal Limbs:
wrist sign

Genitourinary External Genitalia Male:
inguinal hernia

Head And Neck Face:
retrognathia

Cardiovascular Vascular:
aortic dissection
arterial tortuosity
aortic root aneurysm
cerebrovascular aneurysm (in some patients)
fusiform dilation and tortuosity of cerebrovascular arteries

Cardiovascular Heart:
mitral valve prolapse
bicuspid aortic valve (rare)

Skeletal Feet:
flat feet
club feet (in some patients)

Head And Neck Eyes:
hypertelorism (in some patients)
downslanting palpebral fissures (in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
pectus deformity

Skeletal Pelvis:
protrusio acetabularis


Clinical features from OMIM:

614816

Human phenotypes related to Loeys-Dietz Syndrome 4:

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 occasional (7.5%) HP:0000316
2 high palate 32 HP:0000218
3 scoliosis 32 HP:0002650
4 inguinal hernia 32 HP:0000023
5 pes planus 32 HP:0001763
6 emphysema 32 occasional (7.5%) HP:0002097
7 retrognathia 32 HP:0000278
8 joint hyperflexibility 32 HP:0005692
9 bicuspid aortic valve 32 occasional (7.5%) HP:0001647
10 aortic dissection 32 HP:0002647
11 arachnodactyly 32 HP:0001166
12 mitral valve prolapse 32 HP:0001634
13 dural ectasia 32 HP:0100775
14 downslanted palpebral fissures 32 occasional (7.5%) HP:0000494
15 spondylolisthesis 32 occasional (7.5%) HP:0003302
16 talipes equinovarus 32 occasional (7.5%) HP:0001762
17 bruising susceptibility 32 HP:0000978
18 tall stature 32 HP:0000098
19 abnormality of the sternum 32 HP:0000766
20 pneumothorax 32 occasional (7.5%) HP:0002107
21 arterial tortuosity 32 HP:0005116

UMLS symptoms related to Loeys-Dietz Syndrome 4:


wrist sign, steinberg thumb sign

Drugs & Therapeutics for Loeys-Dietz Syndrome 4

Search Clinical Trials , NIH Clinical Center for Loeys-Dietz Syndrome 4

Genetic Tests for Loeys-Dietz Syndrome 4

Genetic tests related to Loeys-Dietz Syndrome 4:

# Genetic test Affiliating Genes
1 Loeys-Dietz Syndrome 4 29 TGFB2

Anatomical Context for Loeys-Dietz Syndrome 4

MalaCards organs/tissues related to Loeys-Dietz Syndrome 4:

41
Skin

Publications for Loeys-Dietz Syndrome 4

Articles related to Loeys-Dietz Syndrome 4:

# Title Authors Year
1
Phenotypic variability and diffuse arterial lesions in a family with Loeys-Dietz syndrome type 4. ( 27440102 )
2016
2
Loeys-Dietz syndrome type 4, caused by chromothripsis, involving the TGFB2 gene. ( 24440784 )
2014
3
Further delineation of Loeys-Dietz syndrome type 4 in a family with mild vascular involvement and a TGFB2 splicing mutation. ( 25163805 )
2014

Variations for Loeys-Dietz Syndrome 4

UniProtKB/Swiss-Prot genetic disease variations for Loeys-Dietz Syndrome 4:

75
# Symbol AA change Variation ID SNP ID
1 TGFB2 p.Arg299Trp VAR_068932 rs863223792
2 TGFB2 p.Arg302Cys VAR_068933 rs869312903
3 TGFB2 p.Pro338His VAR_068934 rs387907278

ClinVar genetic disease variations for Loeys-Dietz Syndrome 4:

6
(show top 50) (show all 172)
# Gene Variation Type Significance SNP ID Assembly Location
1 TGFB2 NM_001135599.3(TGFB2): c.1097C> A (p.Pro366His) single nucleotide variant Pathogenic rs387907278 GRCh37 Chromosome 1, 218610765: 218610765
2 TGFB2 NM_001135599.3(TGFB2): c.1097C> A (p.Pro366His) single nucleotide variant Pathogenic rs387907278 GRCh38 Chromosome 1, 218437423: 218437423
3 TGFB2 NM_001135599.3(TGFB2): c.771C> A (p.Cys257Ter) single nucleotide variant Pathogenic rs398122885 GRCh37 Chromosome 1, 218607723: 218607723
4 TGFB2 NM_001135599.3(TGFB2): c.771C> A (p.Cys257Ter) single nucleotide variant Pathogenic rs398122885 GRCh38 Chromosome 1, 218434381: 218434381
5 TGFB3 NM_003239.4(TGFB3): c.899G> A (p.Arg300Gln) single nucleotide variant Likely pathogenic rs587777617 GRCh37 Chromosome 14, 76429686: 76429686
6 TGFB3 NM_003239.4(TGFB3): c.899G> A (p.Arg300Gln) single nucleotide variant Likely pathogenic rs587777617 GRCh38 Chromosome 14, 75963343: 75963343
7 TGFB2 NM_001135599.2(TGFB2): c.703G> C (p.Val235Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs10482810 GRCh37 Chromosome 1, 218607532: 218607532
8 TGFB2 NM_001135599.2(TGFB2): c.703G> C (p.Val235Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs10482810 GRCh38 Chromosome 1, 218434190: 218434190
9 TGFB3 NM_003239.4(TGFB3): c.559G> A (p.Gly187Ser) single nucleotide variant Uncertain significance rs201063101 GRCh37 Chromosome 14, 76437556: 76437556
10 TGFB3 NM_003239.4(TGFB3): c.559G> A (p.Gly187Ser) single nucleotide variant Uncertain significance rs201063101 GRCh38 Chromosome 14, 75971213: 75971213
11 TGFB3 NM_003239.4(TGFB3): c.487C> T (p.Arg163Trp) single nucleotide variant Uncertain significance rs142601521 GRCh37 Chromosome 14, 76437927: 76437927
12 TGFB3 NM_003239.4(TGFB3): c.487C> T (p.Arg163Trp) single nucleotide variant Uncertain significance rs142601521 GRCh38 Chromosome 14, 75971584: 75971584
13 TGFB3 NM_003239.4(TGFB3): c.293C> T (p.Ser98Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs142047577 GRCh38 Chromosome 14, 75980601: 75980601
14 TGFB3 NM_003239.4(TGFB3): c.293C> T (p.Ser98Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs142047577 GRCh37 Chromosome 14, 76446944: 76446944
15 TGFB3 NM_003239.4(TGFB3): c.898C> T (p.Arg300Trp) single nucleotide variant Pathogenic rs796051885 GRCh37 Chromosome 14, 76429687: 76429687
16 TGFB3 NM_003239.4(TGFB3): c.898C> T (p.Arg300Trp) single nucleotide variant Pathogenic rs796051885 GRCh38 Chromosome 14, 75963344: 75963344
17 TGFB2 NM_003238.3(TGFB2): c.356C> T (p.Pro119Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs149533093 GRCh37 Chromosome 1, 218578520: 218578520
18 TGFB2 NM_003238.3(TGFB2): c.356C> T (p.Pro119Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs149533093 GRCh38 Chromosome 1, 218405178: 218405178
19 TGFB2 NM_003238.3(TGFB2): c.895C> T (p.Arg299Trp) single nucleotide variant Pathogenic/Likely pathogenic rs863223792 GRCh37 Chromosome 1, 218609452: 218609452
20 TGFB2 NM_003238.3(TGFB2): c.895C> T (p.Arg299Trp) single nucleotide variant Pathogenic/Likely pathogenic rs863223792 GRCh38 Chromosome 1, 218436110: 218436110
21 TGFB3 NM_003239.4(TGFB3): c.521T> A (p.Leu174His) single nucleotide variant Uncertain significance rs869025534 GRCh38 Chromosome 14, 75971251: 75971251
22 TGFB3 NM_003239.4(TGFB3): c.521T> A (p.Leu174His) single nucleotide variant Uncertain significance rs869025534 GRCh37 Chromosome 14, 76437594: 76437594
23 TGFB2 NM_001135599.3(TGFB2): c.297C> A (p.Tyr99Ter) single nucleotide variant Pathogenic rs760759052 GRCh37 Chromosome 1, 218520340: 218520340
24 TGFB2 NM_001135599.3(TGFB2): c.297C> A (p.Tyr99Ter) single nucleotide variant Pathogenic rs760759052 GRCh38 Chromosome 1, 218346998: 218346998
25 TGFB2 NM_001135599.2(TGFB2): c.988C> T (p.Arg330Cys) single nucleotide variant Pathogenic/Likely pathogenic rs869312903 GRCh37 Chromosome 1, 218609461: 218609461
26 TGFB2 NM_001135599.2(TGFB2): c.988C> T (p.Arg330Cys) single nucleotide variant Pathogenic/Likely pathogenic rs869312903 GRCh38 Chromosome 1, 218436119: 218436119
27 TGFB2 NM_001135599.3(TGFB2): c.1106_1110delACAAT (p.Tyr369Cysfs) deletion Pathogenic rs398122884 GRCh37 Chromosome 1, 218610774: 218610778
28 TGFB2 NM_001135599.3(TGFB2): c.1106_1110delACAAT (p.Tyr369Cysfs) deletion Pathogenic rs398122884 GRCh38 Chromosome 1, 218437432: 218437436
29 covers 21 genes, none of which curated to show dosage sensitivity NC_000001.10: g.(215588712_?)_(?_222145072)del deletion Pathogenic GRCh37 Chromosome 1, 215588712: 222145072
30 TGFB2 NC_000001.10: g.(216672181_?)_(?_220202575)del deletion Pathogenic GRCh37 Chromosome 1, 216672181: 220202575
31 TGFB2 NM_001135599.3(TGFB2): c.594+38_594+43dupGTTGTT duplication Conflicting interpretations of pathogenicity rs10482769 GRCh38 Chromosome 1, 218405370: 218405375
32 TGFB2 NM_001135599.3(TGFB2): c.594+38_594+43dupGTTGTT duplication Conflicting interpretations of pathogenicity rs10482769 GRCh37 Chromosome 1, 218578712: 218578717
33 TGFB3 NM_003239.4(TGFB3): c.1122C> G (p.Ala374=) single nucleotide variant Benign/Likely benign rs4252345 GRCh37 Chromosome 14, 76425647: 76425647
34 TGFB3 NM_003239.4(TGFB3): c.1122C> G (p.Ala374=) single nucleotide variant Benign/Likely benign rs4252345 GRCh38 Chromosome 14, 75959304: 75959304
35 TGFB3 NM_003239.4(TGFB3): c.873G> A (p.Pro291=) single nucleotide variant Conflicting interpretations of pathogenicity rs370006165 GRCh37 Chromosome 14, 76429712: 76429712
36 TGFB3 NM_003239.4(TGFB3): c.873G> A (p.Pro291=) single nucleotide variant Conflicting interpretations of pathogenicity rs370006165 GRCh38 Chromosome 14, 75963369: 75963369
37 TGFB3 NM_003239.4(TGFB3): c.744C> A (p.Ile248=) single nucleotide variant Conflicting interpretations of pathogenicity rs45477900 GRCh37 Chromosome 14, 76431941: 76431941
38 TGFB3 NM_003239.4(TGFB3): c.744C> A (p.Ile248=) single nucleotide variant Conflicting interpretations of pathogenicity rs45477900 GRCh38 Chromosome 14, 75965598: 75965598
39 TGFB3 NM_003239.4(TGFB3): c.420G> A (p.Glu140=) single nucleotide variant Likely benign rs878854609 GRCh38 Chromosome 14, 75971651: 75971651
40 TGFB3 NM_003239.4(TGFB3): c.420G> A (p.Glu140=) single nucleotide variant Likely benign rs878854609 GRCh37 Chromosome 14, 76437994: 76437994
41 TGFB3 NM_003239.4(TGFB3): c.412T> G (p.Ser138Ala) single nucleotide variant Uncertain significance rs201453600 GRCh38 Chromosome 14, 75971659: 75971659
42 TGFB3 NM_003239.4(TGFB3): c.412T> G (p.Ser138Ala) single nucleotide variant Uncertain significance rs201453600 GRCh37 Chromosome 14, 76438002: 76438002
43 TGFB3 NM_003239.4(TGFB3): c.357A> G (p.Glu119=) single nucleotide variant Likely benign rs748598952 GRCh38 Chromosome 14, 75971714: 75971714
44 TGFB3 NM_003239.4(TGFB3): c.357A> G (p.Glu119=) single nucleotide variant Likely benign rs748598952 GRCh37 Chromosome 14, 76438057: 76438057
45 TGFB3 NM_003239.4(TGFB3): c.179C> T (p.Thr60Met) single nucleotide variant Likely benign rs4252315 GRCh38 Chromosome 14, 75980715: 75980715
46 TGFB3 NM_003239.4(TGFB3): c.179C> T (p.Thr60Met) single nucleotide variant Likely benign rs4252315 GRCh37 Chromosome 14, 76447058: 76447058
47 TGFB3 NM_003239.4(TGFB3): c.82A> C (p.Thr28Pro) single nucleotide variant Uncertain significance rs564013964 GRCh37 Chromosome 14, 76447155: 76447155
48 TGFB3 NM_003239.4(TGFB3): c.82A> C (p.Thr28Pro) single nucleotide variant Uncertain significance rs564013964 GRCh38 Chromosome 14, 75980812: 75980812
49 TGFB3 NM_003239.4(TGFB3): c.34C> T (p.Leu12=) single nucleotide variant Benign/Likely benign rs143612445 GRCh37 Chromosome 14, 76447203: 76447203
50 TGFB3 NM_003239.4(TGFB3): c.34C> T (p.Leu12=) single nucleotide variant Benign/Likely benign rs143612445 GRCh38 Chromosome 14, 75980860: 75980860

Expression for Loeys-Dietz Syndrome 4

Search GEO for disease gene expression data for Loeys-Dietz Syndrome 4.

Pathways for Loeys-Dietz Syndrome 4

Pathways related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

(show all 28)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.08 TGFB2 TGFB3
2
Show member pathways
12.08 TGFB2 TGFB3
3
Show member pathways
12.05 TGFB2 TGFB3
4 12.03 TGFB2 TGFB3
5 11.98 TGFB2 TGFB3
6
Show member pathways
11.96 TGFB2 TGFB3
7
Show member pathways
11.88 TGFB2 TGFB3
8
Show member pathways
11.87 TGFB2 TGFB3
9 11.85 TGFB2 TGFB3
10 11.84 TGFB2 TGFB3
11
Show member pathways
11.81 TGFB2 TGFB3
12 11.78 TGFB2 TGFB3
13 11.75 TGFB2 TGFB3
14 11.72 TGFB2 TGFB3
15 11.66 TGFB2 TGFB3
16
Show member pathways
11.66 TGFB2 TGFB3
17 11.51 TGFB2 TGFB3
18 11.48 TGFB2 TGFB3
19 11.46 TGFB2 TGFB3
20 11.41 TGFB2 TGFB3
21 11.38 TGFB2 TGFB3
22 11.33 TGFB2 TGFB3
23
Show member pathways
11.23 TGFB2 TGFB3
24 11.11 TGFB2 TGFB3
25 11.01 TGFB2 TGFB3
26 10.88 TGFB2 TGFB3
27 10.65 TGFB2 TGFB3
28 10.1 TGFB2 TGFB3

GO Terms for Loeys-Dietz Syndrome 4

Cellular components related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix GO:0031012 8.96 TGFB2 TGFB3
2 platelet alpha granule lumen GO:0031093 8.62 TGFB2 TGFB3

Biological processes related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

(show all 23)
# Name GO ID Score Top Affiliating Genes
1 regulation of cell proliferation GO:0042127 9.61 TGFB2 TGFB3
2 response to hypoxia GO:0001666 9.61 TGFB2 TGFB3
3 platelet degranulation GO:0002576 9.6 TGFB2 TGFB3
4 transforming growth factor beta receptor signaling pathway GO:0007179 9.59 TGFB2 TGFB3
5 BMP signaling pathway GO:0030509 9.58 TGFB2 TGFB3
6 wound healing GO:0042060 9.58 TGFB2 TGFB3
7 roof of mouth development GO:0060021 9.57 TGFB2 TGFB3
8 SMAD protein signal transduction GO:0060395 9.56 TGFB2 TGFB3
9 cell development GO:0048468 9.55 TGFB2 TGFB3
10 regulation of MAPK cascade GO:0043408 9.54 TGFB2 TGFB3
11 inner ear development GO:0048839 9.52 TGFB2 TGFB3
12 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 9.51 TGFB2 TGFB3
13 positive regulation of cell division GO:0051781 9.49 TGFB2 TGFB3
14 positive regulation of epithelial to mesenchymal transition GO:0010718 9.48 TGFB2 TGFB3
15 response to progesterone GO:0032570 9.46 TGFB2 TGFB3
16 positive regulation of protein secretion GO:0050714 9.43 TGFB2 TGFB3
17 odontogenesis GO:0042476 9.4 TGFB2 TGFB3
18 cell-cell junction organization GO:0045216 9.37 TGFB2 TGFB3
19 cell growth GO:0016049 9.32 TGFB2 TGFB3
20 secondary palate development GO:0062009 9.26 TGFB2 TGFB3
21 salivary gland morphogenesis GO:0007435 9.16 TGFB2 TGFB3
22 negative regulation of macrophage cytokine production GO:0010936 8.96 TGFB2 TGFB3
23 uterine wall breakdown GO:0042704 8.62 TGFB2 TGFB3

Molecular functions related to Loeys-Dietz Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytokine activity GO:0005125 9.37 TGFB2 TGFB3
2 growth factor activity GO:0008083 9.32 TGFB2 TGFB3
3 transforming growth factor beta receptor binding GO:0005160 9.26 TGFB2 TGFB3
4 BMP receptor binding GO:0070700 9.16 TGFB2 TGFB3
5 type II transforming growth factor beta receptor binding GO:0005114 8.96 TGFB2 TGFB3
6 type III transforming growth factor beta receptor binding GO:0034714 8.62 TGFB2 TGFB3

Sources for Loeys-Dietz Syndrome 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....